Pyrrolopyridazinone compound

Abstract

The present invention discloses a pyrrolopyridazinone compound represented by the formula (1): useful, for example, as an anti-inflammatory agent or an inhibitor of respiratory tract contraction.

The invention claimed is: 
     
       1. A pyrrolopyridazinone compound represented by the formula (1): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents a C 1 -C 2  alkyl group or a halogeno C 1 -C 2  alkyl group, 
 R 2  represents a C 3 -C 5  cycloalkyl group, a (C 3 -C 5  cycloalkyl)C 1 -C 2  alkyl group or a C 1 -C 3  alkyl group, or a methylene group which constitutes a substituted tetrahydrofuran ring or 3,6-dihydro-2H-pyran ring in combination with a group R 3 , 
 R 3  represents a hydrogen atom, or a methylene group or a cis-vinylene group each of which is a group for constituting a substituted tetrahydrofuran ring or 3,6-dihydro-2H-pyran ring in combination with a group —O—R 2 , 
 R 4  represents a hydrogen atom; a halogen atom; a C 1 -C 8  alkyl group; a C 2 -C 6  alkenyl group; a C 2 -C 6  alkynyl group; a hydroxy C 3 -C 6  alkenyl group; a hydroxy C 3 -C 6  alkynyl group; a C 1 -C 6  alkyl group substituted by a substituent(s) selected from Substituent group (a); a C 3 -C 6  cycloalkyl group which may be substituted by a substituent(s) selected from Substituent group (b); a C 1 -C 3  alkyl group which is substituted by a C 3 -C 6  cycloalkyl group which may be substituted by a substituent(s) selected from Substituent group (b), and which may be substituted by a hydroxy group; an aromatic ring group or heteroaromatic ring group each of which may be substituted by a substituent(s) selected from Substituent group (c); or a C 1 -C 2  alkyl group which is substituted by an aromatic ring group or heteroaromatic ring group each of which may be substituted by a substituent(s) selected from Substituent group (c), and which may be substituted by a hydroxy group; 
 Substituent group (a) represents a halogen atom, a hydroxy group, a cyano group, a carboxy group, a C 1 -C 5  alkoxy group, a halogeno C 1 -C 4  alkoxy group, a C 3 -C 6  cycloalkoxy group, a (C 3 -C 6  cycloalkyl)C 1 -C 2  alkoxy group, a C 1 -C 4  alkoxycarbonyl group, a C 2 -C 4  alkanoyl group, a C 2 -C 4  alkanoyloxy group or a C 1 -C 4  alkyl-substituted amino group, 
 Substituent group (b) represents a hydroxy group or a halogen atom, 
 Substituent group (c) represents a halogen atom, a hydroxy group, a cyano group, a nitro group, a carboxy group, a C 1 -C 5  alkoxy group, a C 1 -C 4  alkoxycarbonyl group, a C 2 -C 4  alkanoyloxy group, a C 1 -C 4  alkyl-substituted amino group or a C 1 -C 4  alkyl group which may be substituted by a substituent(s) selected from the group consisting of a halogen atom, a hydroxy group and a carboxy group, 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
       2. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 R 1  represents a C 1 -C 2  alkyl group or halogeno C 1 -C 2  alkyl group, 
 R 2  represents a C 3 -C 5  cycloalkyl group, (C 3 -C 5  cycloalkyl)C 1 -C 2  alkyl group or C 1 -C 3  alkyl group, 
 R 3  represents a hydrogen atom, and 
 R 4  represents a hydrogen atom; a halogen atom; C 1 -C 8  alkyl group; C 2 -C 6  alkenyl group; C 2 -C 6  alkynyl group; hydroxy C 3 -C 6  alkenyl group; hydroxy C 3 -C 6  alkynyl group; a C 1 -C 6  alkyl group substituted by a substituent(s) selected from Substituent group (a); a C 3 -C 6  cycloalkyl group which may be substituted by a substituent(s) selected from Substituent group (b); a C 1 -C 3  alkyl group which is substituted by a C 3 -C 6  cycloalkyl group which may be substituted by a substituent(s) selected from Substituent group (b), and which may be substituted by a hydroxy group; an aromatic ring group or heteroaromatic ring group each of which may be substituted by a substituent(s) selected from Substituent group (c); or a C 1 -C 2  alkyl group which is substituted by an aromatic ring group or heteroaromatic ring group each of which may be substituted by a group(s) selected from Substituent group (c), and which may be substituted by a hydroxy group; 
 Substituent group (a) represents a halogen atom, a hydroxy group, a cyano group, a carboxy group, C 1 -C 5  alkoxy group, halogeno C 1 -C 4  alkoxy group, C 3 -C 6  cycloalkoxy group, (C 3 -C 6  cycloalkyl)C 1 -C 2  alkoxy group, C 1 -C 4  alkoxycarbonyl group, C 2 -C 4  alkanoyl group, C 2 -C 4  alkanoyloxy group or C 1 -C 4  alkyl-substituted amino group, 
 Substituent group (b) represents a hydroxy group or a halogen atom, 
 Substituent group (c) represents a halogen atom, a hydroxy group, a cyano group, a nitro group, a carboxy group, C 1 -C 5  alkoxy group, C 1 -C 4  alkoxycarbonyl group, C 2 -C 4  alkanoyloxy group, C 1 -C 4  alkyl-substituted amino group or C 1 -C 4  alkyl group which may be substituted by a substituent(s) selected from the group consisting of a halogen atom, a hydroxy group and a carboxy group. 
 
     
     
       3. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 R 1  represents a methyl or difluoromethyl group, 
 R 2  represents a cyclopropyl, cyclobutyl, cyclopentyl, cyclopropylmethyl, cyclobutylmethyl, ethyl or isopropyl group, 
 R 3  represents a hydrogen atom, and 
 R 4  represents a hydrogen atom, chlorine atom, bromine atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, neopentyl, hexyl, 2-ethylbutyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2-chloroethyl, hydroxymethyl, methoxymethyl, ethoxymethyl, isopropoxy-methyl, 2-methoxyethyl, 2-ethoxyethyl, 2-isopropoxyethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, 1-ethylpropoxymethyl, 2-fluoroethoxymethyl, cyclobutoxymethyl, cyclo-propylmethoxymethyl, dimethylaminomethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, cyclobutylmethyl, cyclopropylhydroxymethyl, cyclobutylhydroxymethyl, 2-cyclopropylethyl, 2-cyclobutylethyl, 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, ethynyl, 2-propynyl, 2-butynyl, 4-methyl-2-pentynyl, 1-hydroxy-2-propenyl, phenyl, 2-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chlorophenyl, 4-chlorophenyl, 4-cyanophenyl, 2-thienyl, 3-thienyl, 4-thiazolyl, 5-thiazolyl, 4-pyrazolyl, 6-methoxy-2-pyridyl, 6-methoxy-3-pyridyl, benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 3-carboxybenzyl, 4-carboxybenzyl, 2-thienylmethyl, 5-cyano-2-thienylmethyl, 5-carboxy-2-thienylmethyl, 3-thienylmethyl, 5-cyano-3-thienylmethyl, 5-carboxy-3-thienylmethyl, 2-carboxy-4-thiazolylmethyl, 6-cyano-2-pyridylmethyl, 6-carboxy-2-pyridylmethyl, 6-methoxy-2-pyridylmethyl, 6-cyano-3-pyridylmethyl, 6-carboxy-3-pyridylmethyl, 6-methoxy-3-pyridylmethyl, 2-cyano-3-pyridylmethyl, 2-carboxy-3-pyridylmethyl, 2-cyano-4-pyridylmethyl, 2-carboxy-4-pyridylmethyl, phenethyl, 2-fluorophenethyl, 3-fluorophenethyl, 4-fluorophenethyl, 3-cyanophenethyl, 2-(2-thienyl)ethyl, 2-(6-cyano-2-pyridyl)ethyl, 2-(6-cyano-3-pyridyl)ethyl, 2-(2-cyano-3-pyridyl)ethyl, hydroxyphenylmethyl, (2-fluorophenyl)hydroxymethyl, (3-fluorophenyl)hydroxymethyl or (4-fluorophenyl)hydroxymethyl group. 
 
     
     
       4. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 R 1  represents a difluoromethyl group, 
 R 2  represents a cyclopropyl, cyclobutyl, cyclopentyl, cyclopropylmethyl or isopropyl group, 
 R 3  represents a hydrogen atom, and 
 R 4  represents a hydrogen atom, chlorine atom, bromine atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, neopentyl, hexyl, 2-ethylbutyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2-chloroethyl, hydroxymethyl, methoxymethyl, ethoxymethyl, isopropoxy-methyl, 2-methoxyethyl, 2-ethoxyethyl, 2-isopropoxyethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, 1-ethylpropoxymethyl, 2-fluoroethoxymethyl, cyclobutoxymethyl, cyclo-propylmethoxymethyl, dimethylaminomethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, cyclobutylmethyl, cyclopropylhydroxymethyl, cyclobutylhydroxymethyl, 2-cyclopropylethyl, 2-cyclobutylethyl, 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, ethynyl, 2-propynyl, 2-butynyl, 4-methyl-2-pentynyl, 1-hydroxy-2-propenyl, phenyl, 2-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chlorophenyl, 4-chlorophenyl, 4-cyanophenyl, 2-thienyl, 3-thienyl, 4-thiazolyl, 5-thiazolyl, 4-pyrazolyl, 6-methoxy-2-pyridyl, 6-methoxy-3-pyridyl, benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 3-carboxybenzyl, 4-carboxybenzyl, 2-thienylmethyl, 5-cyano-2-thienylmethyl, 5-carboxy-2-thienylmethyl, 3-thienylmethyl, 5-cyano-3-thienylmethyl, 5-carboxy-3-thienylmethyl, 2-carboxy-4-thiazolylmethyl, 6-cyano-2-pyridylmethyl, 6-carboxy-2-pyridylmethyl, 6-methoxy-2-pyridylmethyl, 6-cyano-3-pyridylmethyl, 6-carboxy-3-pyridylmethyl, 6-methoxy-3-pyridylmethyl, 2-cyano-3-pyridylmethyl, 2-carboxy-3-pyridylmethyl, 2-cyano-4-pyridylmethyl, 2-carboxy-4-pyridylmethyl, phenethyl, 2-fluorophenethyl, 3-fluorophenethyl, 4-fluorophenethyl, 3-cyanophenethyl, 2-(2-thienyl)ethyl, 2-(6-cyano-2-pyridyl)ethyl, 2-(6-cyano-3-pyridyl)ethyl, 2-(2-cyano-3-pyridyl)ethyl, hydroxyphenylmethyl, (2-fluorophenyl)hydroxymethyl, (3-fluorophenyl)hydroxymethyl or (4-fluorophenyl)hydroxymethyl group. 
 
     
     
       5. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 R 1  represents a difluoromethyl group, 
 R 2  represents a cyclopropyl or cyclopropylmethyl group, 
 R 3  represents a hydrogen atom, and 
 R 4  represents a hydrogen atom, chlorine atom, bromine atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, 2-ethylbutyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2-chloroethyl, hydroxymethyl, methoxymethyl, ethoxymethyl, isopropoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, 2-isopropoxyethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, 1-ethylpropoxymethyl, 2-fluoroethoxymethyl, cyclobutoxymethyl, cyclopropylmethoxymethyl, dimethylaminomethyl, cyclopropyl, cyclopropylmethyl, cyclopropylhydroxymethyl, 2-cyclopropylethyl, 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, ethynyl, 2-propynyl, 2-butynyl, 4-methyl-2-pentynyl, 1-hydroxy-2-propenyl, phenyl, 2-thienyl, 3-thienyl, 4-pyrazolyl, benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 3-carboxybenzyl, 2-thienylmethyl, 3-thienylmethyl, 6-methoxy-2-pyridylmethyl, 6-methoxy-3-pyridylmethyl, phenethyl, hydroxyphenylmethyl, (2-fluorophenyl)hydroxymethyl, (3-fluorophenyl)hydroxymethyl or (4-fluorophenyl)hydroxymethyl group. 
 
     
     
       6. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 R 1  represents a difluoromethyl group, 
 R 2  represents a cyclopropyl or cyclopropylmethyl group, 
 R 3  represents a hydrogen atom, and 
 R 4  represents a hydrogen atom, chlorine atom, bromine atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, hydroxymethyl, methoxymethyl, ethoxymethyl, isopropoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, 1-ethylpropoxymethyl, 2-fluoroethoxymethyl, cyclobutoxymethyl, cyclopropylmethoxymethyl, dimethylaminomethyl, cyclopropyl, cyclopropylmethyl, 2-cyclopropylethyl, 2-propenyl, ethynyl, 2-propynyl, 2-butynyl, 4-methyl-2-pentynyl, 1-hydroxy-2-propenyl, phenyl, 4-pyrazolyl, benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 3-carboxybenzyl, 6-methoxy-2-pyridylmethyl, 6-methoxy-3-pyridylmethyl, phenethyl or hydroxyphenylmethyl group. 
 
     
     
       7. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 2 , wherein the pyrrolopyridazinone compound is
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-bromo-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-methyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-ethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-propyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-isopropyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-butyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-isobutyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-pentyl-1,5-dihydropyrrolo[2,3-d]pyriBazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-hexyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-hydroxymethyl-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-methoxymethyl-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(2-methoxyethyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-ethoxymethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(2-ethoxyethyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-isopropoxymethyl-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(2-fluoroethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-cyclopropylmethoxymethyl-1,5-dihydropyrrolo-[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-dimethylaminomethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-cyclopropyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-cyclopropylmethyl-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(2-cyclopropylethyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(2-propenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-ethynyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(2-propynyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-(2-butynyl)-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(4-methyl-2-pentynyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(1-hydroxy-2-propenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-phenyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(4-pyrazolyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-benzyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(2-fluorobenzyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(3-fluorobenzyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(4-fluorobenzyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 3-(2-cyanobenzyl)-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 3-(3-cyanobenzyl)-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 3-(3-carboxybenzyl)-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(6-methoxy-2-pyridylmethyl)-1,5-dihydro-pyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(6-methoxy-3-pyridylmethyl)-1,5-dihydro-pyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-phenethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-hydroxyphenylmethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-ethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)-3-phenyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(4-difluoromethoxy-3-isopropoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(4-difluoromethoxy-3-isopropoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-bromo-2-(4-difluoromethoxy-3-isopropoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-bromo-2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclobutoxy-4-difluoromethoxyphenyl)-3-phenyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(3-cyclopropoxy-4-methoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-bromo-2-(3-cyclopropoxy-4-methoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-butyl-2-(3-cyclopropoxy-4-methoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(3-cyclopropylmethoxy-4-methoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(3-isopropoxy-4-methoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(3-cyclobutoxy-4-methoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopentoxy-4-methoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-isobutoxymethyl-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 3-(sec-butoxymethyl)-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 3-(tert-butoxymethyl)-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, or 
 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-3-(1-ethylpropoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one. 
 
     
     
       8. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 R 1  represents a C 1 -C 2  alkyl group or a halogeno C 1 -C 2  alkyl group, 
 the substituted tetrahydrofuran ring or 3,6-dihydro-2H-pyran ring formed by R 3  in combination with the group —O—R 2  represents a 2,2-(1,2-ethylene)-tetrahydrofuran ring, 2,2-(1,3-propylene)-tetrahydrofuran ring, 2,2-(1,4-butylene)-tetrahydrofuran ring, 2-cyclopropyl-tetrahydrofuran ring, 2-cyclobutyl-tetrahydrofuran ring, 2,2-dimethyl-tetrahydrofuran ring, 6,6-(1,2-ethylene)-3,6-dihydro-2H-pyran ring, 6,6-(1,3-propylene)-3,6-dihydro-2H-pyran ring, 6,6-(1,4-butylene)-3,6-dihydro-2H-pyran ring, 6-cyclopropyl-3,6-dihydro-2H-pyran ring, 6-cyclobutyl-3,6-dihydro-2H-pyran ring or 6,6-dimethyl-3,6-dihydro-2H-pyran ring, 
 R 4  represents a hydrogen atom; a halogen atom; a C 1 -C 8  alkyl group; a C 2 -C 6  alkenyl group; a C 2 -C 6  alkynyl group; a hydroxy C 3 -C 6  alkenyl group; a hydroxy C 3 -C 6  alkynyl group; a C 1 -C 6  alkyl group which is substituted by a substituent(s) selected from Substituent group (a); a C 3 -C 6  cycloalkyl group which may be substituted by a substituent(s) selected from Substituent group (b); a C 1 -C 3  alkyl group which is substituted by a C 3 -C 6  cycloalkyl group which may be substituted by a substituent(s) selected from Substituent group (b) and which may be substituted by a hydroxy group; an aromatic ring group or heteroaromatic ring group each of which may be substituted by a substituent(s) selected from Substituent group (c); or a C 1 -C 2  alkyl group which is substituted by an aromatic ring group or heteroaromatic ring group which may be substituted by a group(s) selected from Substituent group (c), and which may be substituted by a hydroxy group; 
 Substituent group (a) represents a halogen atom, a hydroxy group, a cyano group, a carboxy group, C 1 -C 5  alkoxy group, halogeno C 1 -C 4  alkoxy group, C 3 -C 6  cycloalkoxy group, (C 3 -C 6  cycloalkyl)C 1 -C 2  alkoxy group, C 1 -C 4  alkoxycarbonyl group, C 2 -C 4  alkanoyl group, C 2 -C 4  alkanoyloxy group or C 1 -C 4  alkyl-substituted amino group, 
 Substituent group (b) represents a hydroxy group or a halogen atom, 
 Substituent group (c) represents a halogen atom, a hydroxy group, a cyano group, a nitro group, a carboxy group, a C 1 -C 5  alkoxy group, a C 1 -C 4  alkoxycarbonyl group, a C 2 -C 4  alkanoyloxy group, a C 1 -C 4  alkyl-substituted amino group or a C 1 -C 4  alkyl group which may be substituted by a substituent(s) selected from the group consisting of a halogen atom, a hydroxy group and a carboxy group. 
 
     
     
       9. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 8 , wherein
 R 1  represents a methyl or difluoromethyl group, 
 the substituted tetrahydrofuran ring or 3,6-dihydro-2H-pyran ring formed by R 3  in combination with the group —O—R 2  represents a 2,2-(1,4-butylene)-tetrahydrofuran ring, 6,6-(1,3-propylene)-3,6-dihydro-2H-pyran ring, 6,6-(1,4-butylene)-3,6-dihydro-2H-pyran ring, 6-cyclopropyl-3,6-dihydro-2H-pyran ring or 6,6-dimethyl-3,6-dihydro-2H-pyran ring, 
 R 4  represents a hydrogen atom, chlorine atom, bromine atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, neopentyl, hexyl, 2-ethylbutyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2-chloroethyl, hydroxymethyl, methoxymethyl, ethoxymethyl, isopropoxy-methyl, 2-methoxyethyl, 2-ethoxyethyl, 2-isopropoxyethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, 1-ethylpropoxymethyl, 2-fluoroethoxymethyl, cyclobutoxymethyl, cyclopropylmethoxymethyl, dimethylaminomethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, cyclobutylmethyl, cyclopropylhydroxymethyl, cyclobutylhydroxymethyl, 2-cyclopropylethyl, 2-cyclobutylethyl, 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, ethynyl, 2-propynyl, 2-butynyl, 4-methyl-2-pentynyl, 1-hydroxy-2-propenyl, phenyl, 2-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chlorophenyl, 4-chlorophenyl, 4-cyanophenyl, 2-thienyl, 3-thienyl, 4-thiazolyl, 5-thiazolyl, 4-pyrazolyl, 6-methoxy-2-pyridyl, 6-methoxy-3-pyridyl, benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 3-carboxybenzyl, 4-carboxybenzyl, 2-thienylmethyl, 5-cyano-2-thienylmethyl, 5-carboxy-2-thienylmethyl, 3-thienylmethyl, 5-cyano-3-thienylmethyl, 5-carboxy-3-thienylmethyl, 2-carboxy-4-thiazolylmethyl, 6-cyano-2-pyridylmethyl, 6-carboxy-2-pyridylmethyl, 6-methoxy-2-pyridylmethyl, 6-cyano-3-pyridylmethyl, 6-carboxy-3-pyridylmethyl, 6-methoxy-3-pyridylmethyl, 2-cyano-3-pyridylmethyl, 2-carboxy-3-pyridylmethyl, 2-cyano-4-pyridylmethyl, 2-carboxy-4-pyridylmethyl, phenethyl, 2-fluorophenethyl, 3-fluorophenethyl, 4-fluorophenethyl, 3-cyanophenethyl, 2-(2-thienyl)ethyl, 2-(6-cyano-2-pyridyl)ethyl, 2-(6-cyano-3-pyridyl)ethyl, 2-(2-cyano-3-pyridyl)ethyl, hydroxyphenylmethyl, (2-fluorophenyl)hydroxymethyl, (3-fluorophenyl)hydroxymethyl or (4-fluorophenyl)hydroxymethyl group. 
 
     
     
       10. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 8 , wherein
 R 1  represents a methyl or difluoromethyl group, 
 the substituted tetrahydrofuran ring or 3,6-dihydro-2H-pyran ring formed by R 3  in combination with the group —O—R 2  represents a 2,2-(1,4-butylene)-tetrahydrofuran ring, 6,6-(1,3-propylene)-3,6-dihydro-2H-pyran ring, 6,6-(1,4-butylene)-3,6-dihydro-2H-pyran ring, 6-cyclopropyl-3,6-dihydro-2H-pyran ring or 6,6-dimethyl-3,6-dihydro-2H-pyran ring, 
 R 4  represents a hydrogen atom, chlorine atom, bromine atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, 2-ethylbutyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2-chloroethyl, hydroxymethyl, methoxymethyl, ethoxymethyl, isopropoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, 2-isopropoxyethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, 1-ethylpropoxymethyl, 2-fluoroethoxymethyl, cyclobutoxymethyl, cyclopropylmethoxymethyl, dimethylaminomethyl, cyclopropyl, cyclopropylmethyl, cyclopropylhydroxymethyl, 2-cyclopropylethyl, 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, ethynyl, 2-propynyl, 2-butynyl, 4-methyl-2-pentynyl, 1-hydroxy-2-propenyl, phenyl, 2-thienyl, 3-thienyl, 4-pyrazolyl, benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 3-carboxybenzyl, 2-thienylmethyl, 3-thienylmethyl, 6-methoxy-2-pyridylmethyl, 6-methoxy-3-pyridylmethyl, phenethyl, hydroxyphenylmethyl, (2-fluorophenyl)hydroxylmethyl, (3-fluorophenyl)hydroxymethyl or (4-fluorophenyl)hydroxymethyl group. 
 
     
     
       11. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 8 , wherein
 R 1  represents a difluoromethyl group, 
 the substituted tetrahydrofuran ring or 3,6-dihydro-2H-pyran ring formed by R 3  in combination with the group —O—R 2  represents a 2,2-(1,4-butylene)-tetrahydrofuran ring, 6,6-(1,3-propylene)-3,6-dihydro-2H-pyran ring, 6,6-(1,4-butylene)-3,6-dihydro-2H-pyran ring, 6-cyclopropyl-3,6-dihydro-2H-pyran ring or 6,6-dimethyl-3,6-dihydro-2H-pyran ring, 
 R 4  represents a hydrogen atom, chlorine atom, bromine atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, 2-ethylbutyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2-chloroethyl, hydroxymethyl, methoxymethyl, ethoxymethyl, isopropoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, 2-isopropoxyethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, 1-ethylpropoxymethyl, 2-fluoroethoxymethyl, cyclobutoxymethyl, cyclopropylmethoxymethyl, dimethylaminomethyl, cyclopropyl, cyclopropylmethyl, cyclopropylhydroxymethyl, 2-cyclopropylethyl, 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, ethynyl, 2-propynyl, 2-butynyl, 4-methyl-2-pentynyl, 1-hydroxy-2-propenyl, phenyl, 2-thienyl, 3-thienyl, 4-pyrazolyl, benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 3-carboxybenzyl, 2-thienylmethyl, 3-thienylmethyl, 6-methoxy-2-pyridylmethyl, 6-methoxy-3-pyridylmethyl, phenethyl, hydroxyphenylmethyl, (2-fluorophenyl)hydroxylmethyl, (3-fluorophenyl)hydroxymethyl or (4-fluorophenyl)hydroxymethyl group. 
 
     
     
       12. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 8 , wherein
 R 1  represents a difluoromethyl group, 
 the substituted tetrahydrofuran ring or 3,6-dihydro-2H-pyran ring formed by R 3  in combination with the group —O—R 2  represents a 2,2-(1,4-butylene)-tetrahydrofuran ring, 6,6-(1,3-propylene)-3,6-dihydro-2H-pyran ring, 6,6-(1,4-butylene)-3,6-dihydro-2H-pyran ring, 6-cyclopropyl-3,6-dihydro-2H-pyran ring or 6,6-dimethyl-3,6-dihydro-2H-pyran ring, and 
 R 4  represents a hydrogen atom, chlorine atom, bromine atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, hydroxymethyl, methoxymethyl, ethoxymethyl, isopropoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, isobutoxymethyl, sec-butoxymethyl, tert-butoxymethyl, 1-ethylpropoxymethyl, 2-fluoroethoxymethyl, cyclobutoxymethyl, cyclopropylmethoxymethyl, dimethylaminomethyl, cyclopropyl, cyclopropylmethyl, 2-cyclopropylethyl, 2-propenyl, ethynyl, 2-propynyl, 2-butynyl, 4-methyl-2-pentynyl, 1-hydroxy-2-propenyl, phenyl, 4-pyrazolyl, benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 3-carboxybenzyl, 6-methoxy-2-pyridylmethyl, 6-methoxy-3-pyridylmethyl, phenethyl or hydroxyphenylmethyl group. 
 
     
     
       13. The pyrrolopyridazinone compound or a pharmaceutically acceptable salt thereof according to  claim 8 , wherein the pyrrolopyridazinone compound is
 3-chloro-2-(8-difluoromethoxy-2,2-dimethyl-2H-chromen-5-yl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(8-difluoromethoxy-2,2-dimethyl-2H-chromen-5-yl)-3-methyl-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(8-difluoromethoxy-2,2-dimethyl-2H-chromen-5-yl)-3-ethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-cyclopropyl-2-(8-difluoromethoxy-2,2-dimethyl-2H-chromen-5-yl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, 
 2-(2-cyclopropyl-8-difluoromethoxy-2H-chromen-5-yl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(8-difluoromethoxy-2H-chromen-2-spiro-1′-cyclobutan-5-yl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 3-chloro-2-(8-difluoromethoxy-2H-chromen-2-spiro-1′-cyclopentan-5-yl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(7-difluoromethoxy-2,3-dihydrobenzofuran-2-spiro-1′-cyclopentan-4-yl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, 
 2-(2,3-dihydro-7-methoxybenzofuran-2-spiro-1′-cyclopentan-4-yl)-1,5-dihydropyrrolo[2,3-d]-pyridazin-4-one, or 
 3-chloro-2-(2,3-dihydro-7-methoxybenzofuran-2-spiro-1′-cyclopentan-4-yl)-1,5-dihydropyrrolo-[2,3-d]pyridazin-4-one. 
 
     
     
       14. A pharmaceutical composition which comprises the pyrrolopyridazinone compound according to any one of  claim 1  or a -pharmaceutically acceptable salt thereof as an effective ingredient.